Abstract
Indolent systemic mastocytosis (ISM) is a group of heterogenous diseases characterized by abnormal accumulation of mast cells in at least one organ. ISM can be a cause of osteoporosis. The aim of this study is to determine the prevalence, and the prognosis of ISM in a cohort of patients with osteoporosis. In this monocentric and retrospective study, patients with osteoporosis who did not receive a bone biopsy (cohort 1) and patients that subsequently received a diagnostic bone biopsy for differential diagnosis (cohort 2) are compared with patients who are diagnosed with ISM (cohort 3). A total of 8392 patients are diagnosed with osteoporosis. Out of these patients 1374 underwent a diagnostic bone biopsy resulting in 43 patients with ISM. These figures indicate that ISM is diagnosed in 0.5% of patients with osteoporosis and in 3.1% (men 5.8%) of patients who underwent bone biopsies. Patients with ISM sustained significantly more vertebral fractures in comparison to patients in cohort 2 (4.4 ± 3.6 versus 2.4 ± 2.5 vertebral fractures, p < 0.001) and women were significantly younger compared to cohort 2 (57.3 ± 12 versus 63.6 ± 12 years, p < 0.05). Only 33% showed an involvement of the skin (urticaria pigmentosa). ISM is a rare cause of osteoporosis (0.5%). However, in a subgroup of rather young male patients with osteoporosis the prevalence is more than 5%. Thus, ISM should be considered in premenopausal women and men presenting with vertebral fractures even if urticaria pigmentosa is not present.
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References
Valent P (2013) Mastocytosis: a paradigmatic example of a rare disease with complex biology and pathology. Am J Cancer Res 3(2):159–172
Cohen SS, Skovbo S, Vestergaard H, Kristensen T, Møller M, Bindslev-Jensen C, Fryzek JP, Broesby-Olsen S (2014) Epidemiology of systemic mastocytosis in Denmark. Br J Haematol 166(4):521–528. https://doi.org/10.1111/bjh.12916
Valent P, Akin C, Gleixner K, Sperr W, Reiter A, Arock M, Triggiani M (2019) Multidisciplinary challenges in mastocytosis and how to address with personalized medicine approache. Int J Mol Sci 20:297. https://doi.org/10.3390/ijms20122976
Meyer HJ, Pönisch W, Monecke A, Gundermann P, Surov A (2021) Bone mineral density in patients with systemic mastocytosis: correlations withclinical and histopathological features. Clin Exp Rheumatol 39(1):52–57
Riffel P, Schwaab J, Lutz C, Naumann N, Metzgeroth G, Fabarius A, Schoenberg SO, Hofmann WK, Valent P, Reiter A, Jawhar M (2020) An increased bone mineral density is an adverse prognostic factor in patientswith systemic mastocytosis. J Cancer Res Clin Oncol 146(4):945–951. https://doi.org/10.1007/s00432-019-03119-3
Orsolini G, Viapiana O, Rossini M, Bonifacio M, Zanotti R (2018) Bone disease in mastocytosis. Immunol Allergy Clin N Am 38(3):443–454. https://doi.org/10.1016/j.iac.2018.04.013
Degboé Y, Eischen M, Apoil PA, Mailhol C, Dubreuil P, Hermine O, Paul C, Bulai Livideanu C, Laroche M (2019) Higher prevalence of vertebral fractures in systemic mastocytosis, but not incutaneous mastocytosis and idiopathic mast cell activation syndrome. Osteoporos Int 30(6):1235–1241. https://doi.org/10.1007/s00198-019-04918-7
Acosta-Mérida Á, Ojeda-Bruno S (2019) Multiple vertebral fractures as the first manifestation of systemic mastocytosis. Osteoporos Int 30(5):1121–1124. https://doi.org/10.1007/s00198-019-04897-9
Bouvard B, Pascaretti-Grizon F, Legrand E, Lavigne C, Audran M, Chappard D (2020) Bone lesions in systemic mastocytosis: bone histomorphometry and histopathological mechanisms. Morphologie 104(345):97–108. https://doi.org/10.1016/j.morpho.2020.01.004
Rabenhorst A, Christopeit B, Leja S, Gerbaulet A, Kleiner S, Förster A, Raap U, Wickenhauser C, Hartmann K (2013) Serum levels of bone cytokines are increased in indolent systemic mastocytosis associated with osteopenia or osteoporosis. J Allergy Clin Immunol 132(5):1234–1237. https://doi.org/10.1016/j.jaci.2013.06.019
Seitz S, Barvencik F, Koehne T, Priemel M, Pogoda P, Semler J, Minne H, Pfeiffer M, Zustin J, Püschel K, Eulenburg C, Schinke T, Amling M (2013) Increased osteoblast and osteoclast indices in individuals with systemic mastocytosis. Osteoporos Int 24(8):2325–2334. https://doi.org/10.1007/s00198-013-2305
Rossini M, Zanotti R, Orsolini G, Tripi G, Viapiana O, Idolazzi L, Zamò A, Bonadonna P, Kunnathully V, Adami S, Gatti D (2016) Prevalence, pathogenesis, and treatment options for mastocytosis-related osteoporosis. Osteoporos Int 27(8):2411–2421. https://doi.org/10.1007/s00198-016-3539-1
Laroche M, Livideanu C, Paul C, Cantagrel A (2011) Interferon alpha and pamidronate in osteoporosis with fracture secondary to mastocytosis. Am J Med 124(8):776–778. https://doi.org/10.1016/j.amjmed.2011.02.038
van der Veer E, van der Goot W, de Monchy JG, Kluin-Nelemans HC, van Doormaal JJ (2012) High prevalence of fractures and osteoporosis in patients with indolent systemic mastocytosis. Allergy 67(3):431–438. https://doi.org/10.1111/j.1398-9995.2011.02780
Rossini M, Zanotti R, Bonadonna P, Artuso A, Caruso B, Schena D, Vecchiato D, Bonifacio M, Viapiana O, Gatti D, Senna G, Riccio A, Passalacqua G, Pizzolo G, Adami S (2011) Bone mineral density, bone turnover markers and fractures in patients with indolent systemic mastocytosis. Bone 49(4):880–885. https://doi.org/10.1016/j.bone.2011.07.004
Greene LW, Asadipooya K, Corradi PF, Akin C (2016) Endocrine manifestations of systemic mastocytosis in bone. Rev Endocr Metab Disord 17(3):419–431. https://doi.org/10.1007/s11154-016-9362-3
van der Veer E, Arends S, van der Hoek S, Versluijs JB, de Monchy JGR, Oude Elberink JNG, van Doormaal JJ (2014) Predictors of new fragility fractures after diagnosis of indolent systemic mastocytosis. J Allergy Clin Immunol 134(6):1413–1421. https://doi.org/10.1016/j.jaci.2014.05.003
Zanotti R, Lombardo C, Passalacqua G, Caimmi C, Bonifacio M, De Matteis G, Perbellini O, Rossini M, Schena D, Busa M, Marcotulli MC, Bilò MB, Franchini M, Marchi G, Simioni L, Bonadonna P (2015) Clonal mast cell disorders in patients with severe Hymenoptera venom allergy and normal serum tryptase levels. J Allergy Clin Immunol 136(1):135–139. https://doi.org/10.1016/j.jaci.2014.11.035
Degboé Y, Eischen M, Nigon D, Apoil PA, Mailhol C, Tournier E, Laurent C, Hanssens K, Hermine O, Paul C, Laroche M, Bulai-Livideanu C (2017) Prevalence and risk factors for fragility fracture in systemic mastocytosis. Bone 105:219–225. https://doi.org/10.1016/j.bone.2017.09.005
Rossini M, Zanotti R, Viapiana O, Tripi G, Orsolini G, Idolazzi L, Bonadonna P, Schena D, Escribano L, Adami S, Gatti D (2014) Bone involvement and osteoporosis in mastocytosis. Immunol Allergy Clin N Am 34(2):383–396. https://doi.org/10.1016/j.iac.2014.01.011
Barete S, Assous N, de Gennes C, Grandpeix C, Feger F, Palmerini F, Dubreuil P, Arock M, Roux C, Launay JM, Fraitag S, Canioni D, Billemont B, Suarez F, Lanternier F, Lortholary O, Hermine O, Francès C (2010) Systemic mastocytosis and bone involvement in a cohort of 75 patients. Ann Rheum Dis 69(10):1838–4. https://doi.org/10.1136/ard.2009.124511
Escribano L, Alvarez-Twose I, Sánchez-Muñoz L, Garcia-Montero A, Núñez R, Almeida J, Jara-Acevedo M, Teodósio C, García-Cosío M, Bellas C, Orfao A (2009) Prognosis in adult indolent systemic mastocytosis: a long-term study of the Spanish Network on Mastocytosis in a series of 145 patients. J Allergy Clin Immunol 124(3):514–521. https://doi.org/10.1016/j.jaci.2009.05.003
Delling G, Ritzel H, Werner M (2001) Histological characteristics and prevalence of secondary osteoporosis in systemic mastocytosis. A retrospective analysis of 158 cases. Pathologe 22(2):132–40. https://doi.org/10.1007/s002920000439
Arock M, Sotlar K, Akin C, Broesby-Olsen S, Hoermann G, Escribano L, Kristensen TK, Kluin-Nelemans HC, Hermine O, Dubreuil P, Sperr WR, Hartmann K, Gotlib J, Cross NC, Haferlach T, Garcia-Montero A, Orfao A, Schwaab J, Triggiani M, Horny HP, Metcalfe DD, Reiter A, Valent P (2015) KIT mutation analysis in mast cell neoplasms: recommendations of the European Competence Network on Mastocytosis. Leukemia 29(6):1223–1232. https://doi.org/10.1038/leu.2015.24
Valent P, Escribano L, Broesby-Olsen S, Hartmann K, Grattan C, Brockow K, Niedoszytko M, Nedoszytko B, Oude Elberink JN, Kristensen T, Butterfield JH, Triggiani M, Alvarez-Twose I, Reiter A, Sperr WR, Sotlar K, Yavuz S, Kluin-Nelemans HC, Hermine O, Radia D, van Doormaal JJ, Gotlib J, Orfao A, Siebenhaar F, Schwartz LB, Castells M, Maurer M, Horny HP, Akin C, Metcalfe DD, Arock M, European Competence Network on Mastocytosis (2014) Proposed diagnostic algorithm for patients with suspected mastocytosis: a proposal of the European Competence Network on Mastocytosis. Allergy 69(10):1267–74. https://doi.org/10.1111/all.12436
Valent P, Akin C, Hartmann K, Nilsson G, Reiter A, Hermine O, Sotlar K, Sperr W, Escribano L, George T, Kluin-Nelemans H, Ustun C, Triggiani M, Brockow K, Gotlib J, Orfao A, Schwartz L, Broesby-Olsen S, Bindslev-Jensen C, Kovanen P, Galli S, Austen F, Arber D, Horny H, Arock M, Metcalfe D (2017) Advances in the classification and treatment of mastocytosis: current status and outlook toward the future. Cancer Res 77(6):1261–1270. https://doi.org/10.1158/0008-5472.CAN-16-2234
Rossini M, Zanotti R, Viapiana O, Tripi G, Idolazzi L, Biondan M, Orsolini G, Bonadonna P, Adami S, Gatti D (2014) Zoledronic acid in osteoporosis secondary to mastocytosis. Am J Med 127(11):1127. https://doi.org/10.1016/j.amjmed.2014.06.015
Orsolini G, Gavioli I, Tripi G, Viapiana O, Gatti D, IdolazziL Zanotti R, Rossini M (2017) Denosumab for the treatment of mastocytosis-related osteoporosis: a case series. Calcif Tissue Int 100(6):595–598. https://doi.org/10.1007/s00223-017-0241-z
Wolf E, Röser K, Hahn M, Welkerling H, Delling G (1992) Enzyme and immunhistochemistry on undecalcified bone and bone marrow biopsies after embedding in plastic: a new embedding method for routine application. Virchows Arch A Pathol Anat Histopathol 420:17–24. https://doi.org/10.1007/BF01605979
Arock M, Valent P (2010) Pathogenesis, classification and treatment of mastocytosis: state of the art in 2010 and future perspectives. Expert Rev Hematol 3(4):497–516. https://doi.org/10.1586/ehm.10.42
Nemeth K, Wilson TM, Ren J, Sabatino M, Stroncek DF, Krepuska M, Bai Y, Robey PG, Metcalfe DD, Mezey E (2015) Impaired function of bone marrow stromal cells in systemic mastocytosis. Stem Cell Res 15(1):42–53. https://doi.org/10.1016/j.scr.2015.04.005
Artuso A, Caimmi C, Tripi G, Viapiana O, Bonifacio M, Idolazzi L, Gavioli I, Gatti D, Zanotti R, Rossini M (2017) Longitudinal evaluation of bone mineral density and bone metabolism markers in patients with indolent systemic mastocytosis without osteoporosis. Calcif Tissue Int 100(1):40–46. https://doi.org/10.1007/s00223-016-0198-3
Guillaume N, Desoutter J, Chandesris O, Merlusca L, Henry I, Georgin-Lavialle S, Barete S, Hirsch I, Bouredji D, Royer B, Gruson B, Lok C, Sevestre H, Mentaverri R, Brazier M, Meynier J, Hermine O, Marolleau JP, Kamel S, Pharm D, Damaj G (2013) Bone complications of mastocytosis. Am J Med 126(75):e1-75.e7. https://doi.org/10.1016/j.amjmed.2012.07.018
Cardet JC, Akin C, Lee MJ (2013) Mastocytosis: update on pharmacotherapy and future directions. Expert Opin Pharmacother 14(15):2033–2045. https://doi.org/10.1517/14656566.2013.824424
Black DH, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356(18):1809–1822. https://doi.org/10.1056/NEJMoa067312
Acknowledgements
Authors like to thank Prof. Dr. H. W. Minne, Dr. A.D. Lazarescu, Ch. Hinz, Dr. M. Fischer and B. Ide (Clinic DER FÜRSTENHOF, Bad Pyrmont, Germany) for supporting this study. In addition, authors are especially grateful to Mehrsheed Sinaki, M.D., M.S. (Mayo-Clinic, Rochester, MN, U.S.A.) for reading and reviewing the manuscript.
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MG and HS wrote the manuscript. All authors contributed substantial parts to the elaboration of this study. All authors approved the final version of the manuscript.
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Martin Gehlen, Niels Schmidt, Michael Pfeifer, Subathira Balasingam, Michael Schwarz-Eywill, Anna Maier, Mathias Werner and Heide Siggelkow declare that they have no conflict of interest.
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Retrospective study. For this type of study no formal informed consent is required (see above).
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According to the ethics committee responsible for our clinic, no formal informed consent is required for this type of retrospective study. Informed consent was obtained from each patient before undergoing a bone biopsy.
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This retrospective trial does not include any treatment of humans or animals. Zoledronate was administrated according to the current German guidelines for treatment of osteoporosis.
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Gehlen, M., Schmidt, N., Pfeifer, M. et al. Osteoporosis Caused by Systemic Mastocytosis: Prevalence in a Cohort of 8392 Patients with Osteoporosis. Calcif Tissue Int 109, 685–695 (2021). https://doi.org/10.1007/s00223-021-00887-4
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DOI: https://doi.org/10.1007/s00223-021-00887-4